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BACKGROUND: Possession of one or more apolipoprotein E (APOE) epsilon4 alleles may influence the distribution of atrophy and clinical phenotype. We aimed to assess the influence of APOE genotype on cortical thickness and regional brain volumes in AD (Alzheimer's disease). METHODS: We included 38 patients (9 epsilon4 non-carriers, 23 epsilon4 heterozygotes, 6 epsilon4 homozygotes) and 23 controls. Each subject had 2 magnetic resonance imaging (MRI) scans and a neuropsychological battery. Cortical thickness and isthmus cingulate volume were measured using FreeSurfer; the volumes of the hippocampus, whole brain, and lateral ventricles were calculated using manual and semi-automated volumetry. RESULTS: Compared with controls, cortical thickness was significantly lower: in the bilateral temporal, posterior parietal and occipital regions in non-carriers, in the medial temporal and left parietal regions in heterozygotes, and in the medial temporal lobe in homozygotes. Comparisons between AD subgroups did not show significant differences. A trend for larger brain and isthmus cingulate volumes and smaller hippocampal and ventricular volumes with increasing epsilon4 dose were seen. These differences were supported by neuropsychological profiles. CONCLUSION: These results suggest that APOE genotype may influence the topography of regional atrophy and cortical thinning in AD.